iStopMM: smouldering MM highly prevalent in general population

A large, population-based study showed that smouldering MM is highly prevalent in individuals of 40 years or older. Approximately 1 out of 3 patients with smouldering MM may progress towards MM.

75,422 individuals screened for M-protein and abnormal free light chain ratio

Smouldering MM is an asymptomatic, preliminary condition of MM. Screening for smouldering MM is currently not recommended. Therefore, few patients with MM are diagnosed at the smouldering stage of the disease. However, evidence indicates that treatment initiation at the smouldering stage of MM may be beneficial for health outcomes2,3.

Dr Sigrún Thorsteinsdóttir (University of Iceland, Iceland) and colleagues aimed to map the epidemiological and clinical characteristics of smouldering MM. The large, population-based iStopMM study (NCT03327597) screened 75,422 individuals for M-protein and abnormal free light chain ratio. In total, 3,725 participants displayed abnormal screening results and were randomised to 1 of 3 study arms: no further work-up, guideline-recommended follow-up, or intensive follow-up.

Participants classified into high risk (10%), intermediate risk (26%), or low risk (64%) of progression to MM

Bone marrow sampling was performed in 1,503 participants, resulting in 180 diagnoses of smouldering MM (median age 70; 61% men). The most prevalent isotypes were IgG (57%), IgA (24%), and light chain (14%). The plasma cell burden was mostly low, with 73% of the participants showing plasma cell concentrations of 11-20%. The prevalence of smouldering MM in the total population was estimated at 0.53% in individuals of 40 years or older, with increasing prevalence in older individuals.

The Mayo clinic 2018 risk stratification model for MM was used to classify participants into high risk (10%), intermediate risk (26%), or low risk (64%) of progression to MM. Dr Thorsteinsdóttir argued that treatment initiation at the smouldering MM stage may be included to the guidelines shortly. The high prevalence of smouldering MM in the general population showed the importance of a better screening and risk management for this condition. 

References:
1. Thorsteinsdóttir S, et al. Prevalence of Smoldering Multiple Myeloma: Results from the iStopMM study. O652, ASH 2021 Scientific Sessions, 11-14 December
2. Mateos MV, et al. N Engl J Med. 2013;369(5):438-447
3. Lonial S, et al. J Clin Oncol. 2020;38(11):1126-1137